The present invention relates to a novel treatment for metabolic syndrome and resulting complications, such as obesity, hypertension, hyperlipidemia, hyperinsulinemia and impaired glucose tolerance. In addition, it concerns the use of diazoxide for the treatment of syndrome-X and resulting complications, as well as diabetic complications.
Oral diazoxide (7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-diazoxide) is a nondiuretic congener of the thiazide diuretics which inhibits insulin release from the pancreas (ref. 1). Diazoxide was originally developed for the treatment of hypertension. One of the adverse affects of diazoxide was found to be hyperglycemia, which proved useful in the treatment of hypoglycemia. The hyperglycemia caused by diazoxide is usually transitory and is due to decreased insulin secretion and decreased peripheral utilization of glucose (ref. 2). Diazoxide is now used primarily for the treatment of hypoglycemia due to hyperinsulinism, associated with conditions such as inoperable islet cell adenoma or carcinoma (ref. 3). The drug is currently marketed in the U.S. under the tradename Proglycem.
Syndrome-X is a metabolic syndrome. The term syndrome-X was given by Reaven et al describing a condition characterized by central obesity, and metabolic manifestations including resistance to insulin stimulated glucose uptake, hyperinsulinemia, glucose intolerance (not necessarily diabetes), increased level of very low density lipoprotein triglyceride (VLDL), decreased level of high density lipoprotein cholesterol (HDL) concentrations and hypertension (refs. 4, 5). Each of these characteristic features are considered to be risk factors for development of atherosclerosis and other `old age` diseases. It is believed that syndrome-X is caused by insulin resistance, but no treatment is available at present.
U.S. Pat. No. 5,284,845 discloses the use of oral diazoxide for the normalization of blood glucose and insulin levels in disorders of hyperinsulinemia and diabetes.
However, the background art does not suggest the use of diazoxide for the treatment of syndrome-X, nor for diabetes complications.
No treatment is available for syndrome-X and thus there is a widely recognized need for a drug such as is described in the present invention which is effective in the possible prevention and treatment of syndrome-X and diabetes complications.